dbSNP rs375374643: ATXN7L3:p.Gly243Arg (chr17-44194778-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001382309.1(ATXN7L3):c.727G>A(p.Gly243Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ATXN7L3
NM_001382309.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.44

Publications

1 publications found

Variant links:

Genes affected

ATXN7L3 (HGNC:25416): (ataxin 7 like 3) Enables nuclear receptor coactivator activity. Involved in histone deubiquitination; histone monoubiquitination; and positive regulation of transcription, DNA-templated. Located in nucleus. Part of DUBm complex and SAGA complex. [provided by Alliance of Genome Resources, Apr 2022]

ATXN7L3 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

ATXN7L3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382309.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATXN7L3	NM_001382309.1	MANE Select	c.727G>A	p.Gly243Arg	missense	Exon 11 of 13	NP_001369238.1	Q14CW9-1
ATXN7L3	NM_001382316.1		c.784G>A	p.Gly262Arg	missense	Exon 11 of 13	NP_001369245.1
ATXN7L3	NM_001382308.1		c.748G>A	p.Gly250Arg	missense	Exon 11 of 13	NP_001369237.1	Q14CW9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATXN7L3	ENST00000587097.6	TSL:5 MANE Select	c.727G>A	p.Gly243Arg	missense	Exon 11 of 13	ENSP00000465614.2	Q14CW9-1
ATXN7L3	ENST00000454077.6	TSL:1	c.748G>A	p.Gly250Arg	missense	Exon 10 of 12	ENSP00000397259.1	Q14CW9-2
ATXN7L3	ENST00000389384.8	TSL:1	c.727G>A	p.Gly243Arg	missense	Exon 10 of 12	ENSP00000374035.3	Q14CW9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249160

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461818

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111982

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.00000827

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.32

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.73

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

1.6

PhyloP100

4.4

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.41

Sift

Uncertain

0.015

Sift4G

Uncertain

0.039

Polyphen

1.0

Vest4

0.81

MutPred

0.66

Gain of disorder (P = 0.0303)

MVP

0.53

MPC

1.4

ClinPred

0.91

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.65

Mutation Taster

=29/71

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over